Preparation method and application of inclusion compound of bridged beta-cyclodextrin and resorcinol compound
By using a bridging method to include β-cyclodextrin and resorcinol compounds, the problems of low inclusion rate and poor stability of monomeric β-cyclodextrin were solved, and inclusion complexes with high inclusion rate and strong stability were prepared. These complexes are suitable for skin care products, improving antibacterial and soothing effects and water solubility, and reducing the risk of oxidative degradation.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2026-02-24
- Publication Date
- 2026-04-10
AI Technical Summary
In the prior art, the inclusion rate of monomeric β-cyclodextrin with resorcinol compounds is low and the stability is poor, resulting in insufficient water solubility of resorcinol compounds and easy oxidative degradation, which affects the sustainability of their antibacterial and soothing effects in skin care products.
An inclusion method bridging β-cyclodextrin and resorcinol compounds was adopted. By mixing resorcinol with vitamin E and then ultrasonically treating it with bridging β-cyclodextrin under specific conditions, a multi-component interaction inclusion complex was formed. Combined with low-temperature refrigeration crystallization and vacuum drying steps, a stable inclusion complex was prepared.
It improves inclusion rate and stability, enhances the dispersibility of resorcinol compounds in water-soluble systems, reduces the risk of oxidative degradation, and reduces skin irritation, making it suitable for use in non-pharmaceutical antibacterial and soothing skin care products.
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Abstract
Description
Technical Field
[0001] This invention relates to the field of supramolecular materials technology, and in particular to a method for preparing and applying inclusion complexes that bridge β-cyclodextrin and resorcinol compounds. Background Technology
[0002] Supramolecular inclusion technology is one of the key methods to improve the physicochemical properties of active ingredients. Cyclodextrins and their derivatives, due to their unique hydrophobic cavity structure, can form stable inclusion complexes with various hydrophobic active ingredients, and are widely used in food, daily chemicals, and new materials. Bridged β-cyclodextrin, as a cross-linked polymer derivative of β-cyclodextrin, has a more stable cavity structure and more inclusion sites than monomeric β-cyclodextrin. It is also less prone to dissociation in aqueous solutions, resulting in superior inclusion ability and protective effect for hydrophobic active ingredients, and is gradually becoming a research hotspot in inclusion technology.
[0003] Resorcinol compounds (taking 4-hexylresorcinol as an example) are a class of natural or synthetic active ingredients with significant antibacterial, antioxidant, and skin-soothing properties, making them highly valuable in skin care products. However, resorcinol compounds such as 4-hexylresorcinol are highly lipid-soluble but poorly water-soluble, and their chemical properties are unstable, easily subject to oxidative degradation by factors such as oxygen, light, and temperature. This makes them difficult to disperse evenly in aqueous systems, limiting their application range and severely impacting the utilization rate of active ingredients and product shelf life.
[0004] Existing technologies often employ inclusion modification of monomeric β-cyclodextrin with resorcinol compounds. The hydrophobic cavity of the monomeric β-cyclodextrin accommodates resorcinol molecules to improve their water solubility. However, practical experience shows that the cavity structure of monomeric β-cyclodextrin is singular, and the interaction with resorcinol molecules relies solely on the hydrophobic adsorption of this single cavity. This results in generally low inclusion rates, and the inclusion complex is prone to dissociation during storage or dilution, failing to maintain the long-term stability of the resorcinol compounds and thus affecting the duration of their antibacterial and soothing effects in skin care products.
[0005] Therefore, designing a method for preparing inclusion complexes of bridging β-cyclodextrin and resorcinol compounds with high inclusion rate and strong stability has become an urgent technical challenge. Summary of the Invention
[0006] In view of this, the present invention aims to overcome the problems of low inclusion rate and poor stability of inclusion complexes between monomeric β-cyclodextrin and resorcinol compounds in the prior art, which leads to insufficient water solubility and easy oxidative degradation of resorcinol compounds. The present invention provides a method for preparing inclusion complexes of bridged β-cyclodextrin and resorcinol compounds with high inclusion rate and strong stability, the method comprising the following steps: S1: Mix resorcinol compounds and vitamin E at a mass ratio of (6-10):1 until homogeneous, and record this mixture as mixture A; S2: Measure deionized water, heat it to 50-60℃, add dried bridged β-cyclodextrin at a solid-liquid ratio of 0.06-0.09 g / mL, stir at 140-190 rpm until completely dissolved, and obtain a saturated solution, denoted as solution B; S3: Dissolve mixture A in anhydrous ethanol and denote it as solution C. Add solution C dropwise to solution B, maintain the temperature at 50-60℃ and stir for 25-35 minutes, then sonicate for 40-55 minutes. S4: After sonication, allow the mixed solution to cool naturally to room temperature, then refrigerate at 1-3°C for 7-11 hours to allow the inclusion complex to crystallize out. S5: Collect the crystals by vacuum filtration, wash them twice each with anhydrous ethanol and deionized water, collect the filter cake, dry it under vacuum at 55-65℃ for 3-5 hours, pulverize it and sieve it to obtain the inclusion compound product.
[0007] Furthermore, in the above method, the bridged β-cyclodextrin is an epichlorohydrin cross-linked bridged β-cyclodextrin with a molecular weight of 5000-10000 Da and a purity of ≥98%.
[0008] Furthermore, the bridging β-cyclodextrin is dried under vacuum at 75–85°C for 1.5–2.5 h.
[0009] Furthermore, in the above method, the molar ratio of bridged β-cyclodextrin to resorcinol compounds is 1:(0.7-1.1).
[0010] Furthermore, in step S3, the power of the ultrasonic treatment is 140–190W, and the frequency is 38–42kHz.
[0011] Furthermore, in step S3, the amount of anhydrous ethanol used is 22-28 mL.
[0012] Furthermore, in step S5, the filtration is performed using a Buchner funnel, and the washing volume of anhydrous ethanol and deionized water is 8-14 mL per wash.
[0013] Furthermore, in step S5, the sieve mesh is 75-85 mesh.
[0014] This invention also discloses the application of inclusion complexes of bridged β-cyclodextrin and resorcinol compounds in the preparation of non-pharmaceutical antibacterial soothing skin care products.
[0015] Furthermore, the antibacterial and soothing skin care product is a topical, non-pharmaceutical product.
[0016] The beneficial effects of this invention are as follows: First, bridged β-cyclodextrin, as a cross-linked polymer, has more inclusion sites and a more stable cavity structure compared to monomeric β-cyclodextrin. It forms multi-component interactions with resorcinol compounds through hydrophobic interactions and van der Waals forces, rather than adsorption and binding within a single cavity. This binding mechanism enhances the structural stability of the inclusion complex, reduces dissociation during storage or application, and simultaneously improves the loading efficiency of the active ingredient during inclusion.
[0017] Second, in this invention, the cavity structure of the bridged β-cyclodextrin can effectively encapsulate resorcinol compounds, reducing their contact with external environmental factors such as oxygen and light, and lowering the risk of oxidative degradation of the active ingredients. Simultaneously, the cross-linked polymer structure improves the water solubility of resorcinol compounds, enabling them to disperse uniformly in aqueous systems and avoiding the problem of poor dissolution of lipid-soluble components. This characteristic broadens the application scenarios of resorcinol compounds in skin care products.
[0018] Thirdly, in this invention, the bridged β-cyclodextrin itself possesses excellent biocompatibility. The inclusion complex formed with resorcinol compounds retains the antibacterial and soothing properties of the active ingredients while reducing the direct skin irritation of lipid-soluble resorcinol compounds, making it more suitable for topical skin care applications. The preparation process employs gentle solution mixing, ultrasound-assisted crystallization, and low-temperature refrigeration, eliminating the need for harsh conditions such as high temperature and high pressure. This avoids damage to the structure of active ingredients from extreme environments, simplifies the production process, reduces reliance on specialized equipment, facilitates large-scale production, and ensures the safety and practicality of antibacterial and soothing skin care products. Detailed Implementation
[0019] The technical solution of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art are within the protection scope of the present invention.
[0020] Example 1 A method for preparing inclusion complexes of bridging β-cyclodextrin and resorcinol compounds, comprising the following steps: S1: Weigh 4-hexylresorcinol and vitamin E in a mass ratio of 6:1, place them in a beaker and mix them evenly. This mixture is called mixture A. S2: Accurately measure 100mL of deionized water and pour it into a three-necked flask. Heat to 50℃, add 6g of dried epichlorohydrin cross-linked bridged β-cyclodextrin, and start the stirring device to continuously stir at 140rpm until the bridged β-cyclodextrin is completely dissolved, resulting in a clear and transparent saturated solution, which is denoted as solution B. S3: Add mixture A to 22 mL of anhydrous ethanol and stir until completely dissolved. This solution is called solution C. Slowly add solution C to solution B through a constant pressure dropping funnel. Maintain the reaction temperature at 50°C and continue stirring for 25 min. Then turn on the ultrasonic device and sonicate for 40 min. S4: After ultrasonic treatment, turn off the heating and stirring devices, allow the mixed solution to cool naturally to room temperature, then transfer it to a sealed container and refrigerate it in a 1°C refrigerator for 7 hours to allow the inclusion complex to fully crystallize and precipitate. S5: The crystallization liquid was filtered using a Buchner funnel to collect the crystals; the crystals were washed once with 8 mL of anhydrous ethanol, allowed to stand for 3 min, filtered, and then washed once with 8 mL of deionized water. This washing operation was repeated twice; the filtered cake was collected and placed in a vacuum drying oven at 55℃ for 3 h. After drying, it was pulverized with a pulverizer and passed through a 75-mesh sieve to obtain a white powdery inclusion compound product.
[0021] The drying conditions were as follows: the bridged β-cyclodextrin was vacuum dried at 75°C for 1.5 h.
[0022] The molar ratio of bridged β-cyclodextrin to 4-hexylresorcinol is 1:0.7.
[0023] The ultrasonic treatment power was 140W and the frequency was 38kHz.
[0024] Example 2 A method for preparing inclusion complexes of bridging β-cyclodextrin and resorcinol compounds, comprising the following steps: S1: Weigh 4-hexylresorcinol and vitamin E at a mass ratio of 8:1, place them in a beaker and mix them evenly. This mixture is called mixture A. S2: Accurately measure 100mL of deionized water and pour it into a three-necked flask. Heat to 55℃, add 7.5g of dried epichlorohydrin cross-linked bridged β-cyclodextrin, and start the stirring device to continuously stir at 165rpm until the bridged β-cyclodextrin is completely dissolved, resulting in a clear and transparent saturated solution, which is denoted as solution B. S3: Add mixture A to 25 mL of anhydrous ethanol and stir until completely dissolved. This solution is called solution C. Slowly add solution C to solution B through a constant pressure dropping funnel. Maintain the reaction temperature at 55 °C and continue stirring for 30 min. Then turn on the ultrasonic device and sonicate for 48 min. S4: After ultrasonic treatment, turn off the heating and stirring devices, allow the mixed solution to cool naturally to room temperature, then transfer it to a sealed container and refrigerate it in a 2°C refrigerator for 9 hours to allow the inclusion complex to fully crystallize and precipitate. S5: The crystallization liquid was filtered using a Buchner funnel to collect the crystals; the crystals were washed once with 11 mL of anhydrous ethanol, allowed to stand for 3 min, filtered, and then washed once with 11 mL of deionized water. This washing operation was repeated twice; the filter cake was collected and placed in a vacuum drying oven at 60℃ for 4 h. After drying, it was pulverized with a pulverizer and passed through an 80-mesh sieve to obtain a white powdery inclusion compound product. The drying conditions were as follows: the bridged β-cyclodextrin was vacuum dried at 80°C for 2 hours.
[0025] The molar ratio of bridged β-cyclodextrin to 4-hexylresorcinol is 1:0.9.
[0026] The ultrasonic treatment power was 165W and the frequency was 40kHz.
[0027] Example 3 A method for preparing inclusion complexes of bridging β-cyclodextrin and resorcinol compounds, comprising the following steps: S1: Weigh 4-hexylresorcinol and vitamin E at a mass ratio of 10:1, place them in a beaker and mix them evenly. This mixture is denoted as mixture A, in which the molar ratio of bridged β-cyclodextrin to 4-hexylresorcinol is 1:1.1. S2: Accurately measure 100mL of deionized water and pour it into a three-necked flask. Heat the flask to 60℃, add 9g of dried epichlorohydrin cross-linked bridged β-cyclodextrin, and start the stirring device to continuously stir at 190rpm until the bridged β-cyclodextrin is completely dissolved, resulting in a clear and transparent saturated solution, which is denoted as solution B. S3: Add mixture A to 28 mL of anhydrous ethanol and stir until completely dissolved, and record this as solution C; slowly add solution C to solution B through a constant pressure dropping funnel, maintain the reaction temperature at 60 °C and continue stirring for 35 min, then turn on the ultrasonic device and sonicate for 55 min; S4: After ultrasonic treatment, turn off the heating and stirring devices, allow the mixed solution to cool naturally to room temperature, then transfer it to a sealed container and refrigerate it in a 3°C refrigerator for 11 hours to allow the inclusion complex to fully crystallize and precipitate. S5: The crystallization liquid was filtered using a Buchner funnel to collect the crystals; the crystals were washed once with 14 mL of anhydrous ethanol, allowed to stand for 3 min, filtered, and then washed once with 14 mL of deionized water. This washing operation was repeated twice; the filter cake was collected and placed in a vacuum drying oven at 65 °C for 5 h. After drying, it was pulverized with a pulverizer and passed through an 85-mesh sieve to obtain a white powdery inclusion compound product. The drying conditions were as follows: the bridged β-cyclodextrin was vacuum dried at 85°C for 2.5 h.
[0028] The ultrasonic treatment power was 190W and the frequency was 42kHz.
[0029] Example 4 A method for preparing inclusion complexes of bridging β-cyclodextrin and resorcinol compounds, comprising the following steps: S1: Weigh 4-hexylresorcinol and vitamin E in a mass ratio of 7:1, place them in a beaker and mix them evenly. This mixture is called mixture A. S2: Accurately measure 100mL of deionized water and pour it into a three-necked flask. Heat to 52℃, add 6.5g of dried epichlorohydrin cross-linked bridged β-cyclodextrin, and start the stirring device to continuously stir at 150rpm until completely dissolved, to obtain a clear and transparent saturated solution, which is denoted as solution B. S3: Add mixture A to 23 mL of anhydrous ethanol and stir until completely dissolved. This solution is called solution C. Slowly add solution C to solution B through a constant pressure dropping funnel. Stir at 52 °C for 28 min, then turn on the ultrasonic device and sonicate for 42 min. S4: After sonication, allow the mixture to cool naturally to room temperature, transfer it to a sealed container, and refrigerate it at 1.5℃ for 8 hours to allow the inclusion complex to fully crystallize and precipitate. S5: The crystals were collected by vacuum filtration using a Buchner funnel; the crystals were washed twice with 9 mL of anhydrous ethanol and then twice with 9 mL of deionized water, and the mixture was allowed to stand for 3 min after each wash before vacuum filtration; the filter cake was collected, dried in a vacuum drying oven at 58℃ for 3.5 h, pulverized, and passed through a 78-mesh sieve to obtain a white powdery inclusion complex product. The drying conditions were as follows: the bridged β-cyclodextrin was vacuum dried at 78°C for 1.8 h.
[0030] The molar ratio of bridged β-cyclodextrin to 4-hexylresorcinol is 1:0.8.
[0031] The ultrasonic treatment power was 150W and the frequency was 39kHz.
[0032] Example 5 A method for preparing inclusion complexes of bridging β-cyclodextrin and resorcinol compounds, comprising the following steps: S1: Weigh 4-hexylresorcinol and vitamin E at a mass ratio of 9:1, place them in a beaker and mix them evenly. This mixture is called mixture A. S2: Accurately measure 100mL of deionized water and pour it into a three-necked flask. Heat to 58℃, add 8.5g of dried epichlorohydrin cross-linked bridged β-cyclodextrin, and start the stirring device to continuously stir at 180rpm until completely dissolved, to obtain a clear and transparent saturated solution, which is denoted as solution B. S3: Add mixture A to 27 mL of anhydrous ethanol and stir until completely dissolved. This solution is called solution C. Slowly add solution C to solution B through a constant pressure dropping funnel, and stir at 58 °C for 32 min. Then turn on the ultrasonic device and sonicate for 52 min. S4: After sonication, allow the mixture to cool naturally to room temperature, transfer it to a sealed container, and refrigerate it at 2.5℃ for 10 hours to allow the inclusion complex to fully crystallize and precipitate. S5: The crystals were collected by vacuum filtration using a Buchner funnel; the crystals were washed twice with 13 mL of anhydrous ethanol and then twice with 13 mL of deionized water. After each washing, the crystals were allowed to stand for 3 min before vacuum filtration. The filter cake was collected, dried in a vacuum drying oven at 63 °C for 4.5 h, pulverized, and passed through an 83-mesh sieve to obtain a white powdery inclusion complex product.
[0033] The drying conditions were as follows: the bridged β-cyclodextrin was vacuum dried at 82°C for 2.2 h.
[0034] The molar ratio of bridged β-cyclodextrin to 4-hexylresorcinol is 1:1.0.
[0035] The ultrasonic treatment power was 180W and the frequency was 41kHz.
[0036] The raw materials used in the above embodiments were as follows: epichlorohydrin cross-linked bridged β-cyclodextrin (molecular weight 5000-10000 Da, purity ≥98%) was purchased from Shanghai Yuanye Biotechnology Co., Ltd.; 4-hexylresorcinol (purity ≥99%) was obtained from Wuhan Yuancheng Gongchuang Technology Co., Ltd.; vitamin E (analytical grade, purity ≥96%) was purchased from Sinopharm Chemical Reagent Co., Ltd.; and anhydrous ethanol (analytical grade, purity ≥99.7%) was obtained from Jiangsu Hualun Chemical Co., Ltd.
[0037] Comparative Example 1 In step S1, the monomeric β-cyclodextrin is used to replace the epichlorohydrin cross-linked bridged β-cyclodextrin; the remaining raw material ratios, operating steps and parameters are the same as in Example 1.
[0038] Comparative Example 2 In step S3, no ultrasonic treatment is performed; instead, the mixture is stirred at 50°C for 25 minutes and then stirred at a constant temperature for another 40 minutes. The remaining raw material ratios, operating steps, and parameters are the same as in Example 1.
[0039] Comparative Example 3 In step S1, vitamin E is not added, and mixture A is prepared using only 4-hexylresorcinol; the remaining raw material ratios, operating steps and parameters are the same as in Example 1.
[0040] Comparative Example 4 In step S1, no epichlorohydrin-crosslinked bridged β-cyclodextrin is added; in step S2, no cyclodextrin-like substances are added; the remaining raw material ratios, operating steps, and parameters are the same as in Example 1.
[0041] Performance testing I. Inclusion Rate Test Weigh 0.1000 g of each of the inclusion complex products prepared in the examples and comparative examples, place them in 50 mL centrifuge tubes, add 20.0 mL of anhydrous ethanol to each tube, extract by sonication for 30 min, centrifuge at 10000 rpm for 10 min, and take the supernatant and filter it through a 0.45 μm organic phase filter membrane. Separately weigh 0.0100 g of 4-hexylresorcinol standard and dilute to 100 mL with anhydrous ethanol to prepare a standard stock solution with a concentration of 100 μg / mL. Then dilute this stock solution to prepare a series of standard solutions with concentrations of 20 μg / mL, 40 μg / mL, 60 μg / mL, and 80 μg / mL. Use a high-performance liquid chromatograph (HPLC) equipped with a C18 column (4.6 mm × 250 mm, 5 μm), set the column temperature to 30 °C, the mobile phase to methanol-water = 80:20 (v / v), the flow rate to 1.0 mL / min, the detection wavelength to 275 nm, and the injection volume to 20 μL. Plot a standard curve and calculate the regression equation.
[0042] The sample supernatant was injected into the chromatograph under the same conditions. The actual content of 4-hexylresorcinol in the inclusion complex was calculated by substituting the peak area into the regression equation. The inclusion rate was calculated by the formula η=(m1 / m0)×100%.
[0043] Where η is the inclusion rate, m1 is the actual content of 4-hexylresorcinol in the inclusion compound, and m0 is the theoretical feed amount of 4-hexylresorcinol; the results are shown in Table 1.
[0044] II. Water solubility test According to GB / T14454.1-2008 "Determination of Solubility of Fragrances".
[0045] Measure 100.0 mL of deionized water into a 250 mL beaker, place it in a constant temperature water bath and adjust the temperature to 25℃±0.5℃, then start the magnetic stirrer at 300 rpm. Weigh out the inclusion complex products from the examples and comparative examples, adding 0.10 g at a time, stirring for 10 min until completely dissolved, then continue adding until a visible insoluble precipitate appears. Stop adding and record the maximum dissolved mass m. Calculate the solubility using the formula S=m / 100 (S is the solubility, unit g / 100 mL); simultaneously, use pure 4-hexylresorcinol as a blank control and test its solubility using the same method; the results are shown in Table 1.
[0046] III. Skin Irritation Test According to GB / T21604-2008 "Skin Irritation / Corrosion Tests for Chemicals": Three healthy New Zealand white rabbits, weighing 2.0-2.5 kg, were selected. Twenty-four hours before the test, symmetrical hair was removed from both sides of the spine on the back, with a removal area of 3 cm × 3 cm on each side, ensuring no skin damage after hair removal. The left hair removal area was the test group, where 0.2 mL of the inclusion complex aqueous solution (5% concentration) prepared in Example 2 was applied, covered with sterile gauze and fixed. The right hair removal area was the control group, where an equal volume of physiological saline was applied, and the treatment was the same. Apply the product continuously for 14 days, once a day. Before each application, observe and record whether the skin shows any irritation reactions such as erythema, edema, erosion, or crusting. Use a standard scoring system (erythema: 0 = none, 1 = mild, 2 = moderate, 3 = severe; edema: 0 = none, 1 = mild, 2 = moderate, 3 = severe) to calculate the average irritation score and assess the irritation level (0-0.5 points for no irritation, 0.6-2.0 points for mild irritation, 2.1-4.0 points for moderate irritation, and 4.1-8.0 points for severe irritation). The results are shown in Table 1.
[0047] IV. Antibacterial Performance Test According to GB / T20944.3-2008 "Evaluation of Antimicrobial Properties of Textiles - Part 3: Shaking Method": The inclusion complex from Example 2 was prepared into a 5% (mass concentration) aqueous solution. 10.0 mL of this solution was added to a sterile Erlenmeyer flask, and 1.0 mL of Staphylococcus aureus (ATCC6538) and Escherichia coli (ATCC8099) bacterial suspension at a concentration of (1.0±0.2)×10⁵ CFU / mL was added. The flask was then placed in a constant temperature shaking incubator at 37℃±1℃ and incubated at 150 rpm for 24 h. A blank control group (10 mL sterile water + 1 mL bacterial suspension) and a negative control group (10 mL 5% inclusion complex aqueous solution + 1 mL sterile water) were also set up and incubated under the same conditions. After incubation, 0.1 mL of the sample solution was serially diluted (10⁻¹, 10⁻², 10⁻³). 0.1 mL of each diluted solution was evenly spread onto nutrient agar medium and incubated at 37℃ for 24 h before plate counting. The antibacterial rate was calculated using the formula A=(BC) / B×100% (A is the antibacterial rate, B is the number of colonies in the blank control group, and C is the number of colonies in the sample group); the results are shown in Table 1.
[0048] V. Stability Testing Each sample was sealed in an aluminum foil composite bag, with each bag containing 5g of sample. The bags were placed in an accelerated aging chamber and stored under the following conditions: temperature 40℃±1℃ and relative humidity 75%±5% for 6 months. During this period, the samples were protected from moisture, light, and contamination.
[0049] Inclusion rate and retention rate: After storage, the sample was equilibrated at 25℃±2℃ for 2 hours. 0.1000g of sample was accurately weighed and placed in a 50mL centrifuge tube. 20.0mL of anhydrous ethanol was added, and the sample was extracted by sonication for 30min. Then, it was centrifuged at 10000rpm for 10min. The supernatant was filtered through a 0.45μm organic phase filter membrane, and the filtrate was collected. Using the standard curve and regression equation from the original inclusion rate test, a high-performance liquid chromatograph (HPLC) with a C18 column was used. The column temperature was 30℃, the mobile phase was methanol and water (volume ratio: 80:20), the flow rate was 1.0mL / min, the detection wavelength was 275nm, and the injection volume was 20μL. The actual content of 4-hexylresorcinol in the filtrate was determined. The test results are shown in Table 1.
[0050] The original binding rate formula is used to calculate the binding rate η2 after storage: η2 = (m1' / m0) × 100%; Inclusion retention rate = (η2 / η1) × 100%; Where m1' is the actual content of 4-hexylresorcinol in the inclusion complex after storage, m0 is the theoretical amount of 4-hexylresorcinol fed in, and η1 is the initial inclusion rate before storage.
[0051] Accelerates water solubility after 6 months of storage: Take out the stored sample and equilibrate it at 25℃±2℃ for 2 hours; measure 100.0 mL of deionized water into a 250 mL beaker, place it in a constant temperature water bath, adjust the temperature to 25℃±0.5℃, and start the magnetic stirrer to stir continuously at 300 rpm; weigh the stored sample, add 0.10 g each time, stir for 10 min until completely dissolved, and continue adding until a visible insoluble precipitate appears, then stop adding and record the maximum dissolved mass m'; The solubility S' after storage was calculated according to the original water solubility formula: S'=m' / 100 (unit: g / 100mL); the results are shown in Table 1.
[0052] Table 1 As shown in Table 1, the superior performance of Examples 1-3 of this invention stems from the combined addition of epichlorohydrin cross-linked bridged β-cyclodextrin, ultrasonic-assisted inclusion process, and vitamin E. Compared to monomeric cyclodextrin, epichlorohydrin cross-linked bridged β-cyclodextrin possesses more inclusion sites and a more stable cavity structure, enabling it to form multi-component interactions with 4-hexylresorcinol and improve the loading efficiency of the active ingredient. Ultrasonic treatment accelerates the diffusion of 4-hexylresorcinol molecules into the cyclodextrin cavity through mechanical vibration and cavitation effects, promoting a complete inclusion reaction. Vitamin E not only inhibits the oxidative degradation of 4-hexylresorcinol but also moderately regulates the system compatibility, significantly improving the inclusion rate and water solubility of the inclusion complex, while reducing the direct skin irritation of 4-hexylresorcinol and allowing the antibacterial activity to be stably exerted.
[0053] Comparative Example 1 exhibits poor performance due to the structural limitations of the monomer β-cyclodextrin. The monomer β-cyclodextrin possesses only a single cavity structure, and its interaction with 4-hexylresorcinol relies solely on a single hydrophobic adsorption. Insufficient inclusion sites result in limited loading capacity of the active ingredient, and the formed binding structure is prone to dissociation, thus affecting water solubility and the persistence of antibacterial effects. Furthermore, it fails to effectively reduce the skin irritation of 4-hexylresorcinol.
[0054] Comparative Example 2 did not undergo ultrasonic treatment. Ultrasonic treatment is a key process to promote the full progress of the inclusion reaction. Its cavitation effect can break down the intermolecular force barriers, allowing for more uniform contact and deeper action between 4-hexylresorcinol and the bridged β-cyclodextrin. Simply extending the stirring time cannot achieve the same level of mass transfer efficiency, resulting in insufficient inclusion reaction, uneven inclusion complex structure, and consequently, low inclusion rate and insufficient water solubility. Furthermore, the uneven system increases skin irritation, and the antibacterial activity decreases due to unstable release of the active ingredient.
[0055] Comparative Example 3 lacked Vitamin E. Vitamin E, as an antioxidant, inhibits the oxidative degradation of 4-hexylresorcinol, reducing the formation of irritating oxidation products. On the other hand, as an inclusion agent, it regulates the polarity matching of guest molecules, promoting the entry of 4-hexylresorcinol into the hydrophobic cavity. The lack of Vitamin E resulted in a double negative effect of increased free 4-hexylresorcinol and the formation of oxidation products. Although the impact on inclusion rate and water solubility was relatively small, the overall performance was still inferior to the examples.
[0056] Comparative Example 4 performed the worst, essentially due to the lack of a bridging β-cyclodextrin inclusion carrier. Bridging β-cyclodextrin is the core component for improving the water solubility and protecting the structure of 4-hexylresorcinol. Without this carrier, 4-hexylresorcinol retains its strong lipophilic properties, making it difficult to disperse in aqueous systems. Furthermore, lacking the protection of the cavity structure, it is easily oxidized and degraded. Consequently, it cannot exert an effective antibacterial effect, and the directly exposed lipophilic molecules can cause skin irritation, completely failing to meet application requirements.
[0057] To investigate the application of the inclusion complex in the preparation of non-pharmaceutical antibacterial and soothing skin care products, it was prepared as a spray. The specific steps were as follows: 5.0g of the inclusion complex prepared in Example 2, 95.0g of deionized water, and 0.1g of medical-grade preservative (ethylparaben) were taken. The inclusion complex was added to the deionized water, and a magnetic stirrer was started and stirred at 300 rpm for 15 minutes until completely dissolved. The preservative was added, and stirring was continued for 5 minutes to mix evenly. The mixed solution was filtered through a 0.22μm organic phase filter membrane to remove impurities. The filtered clear solution was filled into a sterile spray bottle and sealed to obtain the antibacterial and soothing spray.
[0058] Performance test results are as follows: spray pH value 6.4; no stratification or precipitation after 6 months of storage at room temperature; antibacterial rate of 91.8% against Staphylococcus aureus and 90.9% against Escherichia coli.
[0059] The bridged β-cyclodextrin and 4-hexylresorcinol inclusion complex prepared in this invention perfectly meets the application requirements of antibacterial and soothing skin care products due to its excellent water solubility, low irritation, and stable antibacterial properties. It can be easily prepared into topical non-pharmaceutical products such as sprays and gels without complex subsequent processing, and can stably exert its efficacy in scenarios such as relieving itching from mosquito bites, soothing minor abrasions, and alleviating daily dryness and itching. This solves the problems of poor water solubility and easy loss of activity of traditional 4-hexylresorcinol in skin care products, while ensuring the safety and practicality of the products, providing reliable technical support for the large-scale application of 4-hexylresorcinol in the daily chemical industry.
[0060] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., within the spirit and principles of the present invention should be included within the protection scope of the present invention.
Claims
1. A method for preparing inclusion complexes bridging β-cyclodextrin and resorcinol compounds, characterized in that, Includes the following steps, S1: Mix resorcinol compounds and vitamin E at a mass ratio of (6-10):1 until homogeneous, and record this mixture as mixture A; S2: Measure deionized water, heat it to 50-60℃, add dried bridged β-cyclodextrin at a solid-liquid ratio of 0.06-0.09 g / mL, stir at 140-190 rpm until completely dissolved, and obtain a saturated solution, denoted as solution B; S3: Dissolve mixture A in anhydrous ethanol and denote it as solution C. Add solution C dropwise to solution B, maintain the temperature at 50-60℃ and stir for 25-35 minutes, then sonicate for 40-55 minutes. S4: After sonication, allow the mixed solution to cool naturally to room temperature, then refrigerate at 1-3°C for 7-11 hours to allow the inclusion complex to crystallize out. S5: Collect the crystals by filtration, wash them twice each with anhydrous ethanol and deionized water, collect the filter cake, dry it under vacuum at 55-65℃ for 3-5 hours, pulverize it and sieve it to obtain the inclusion compound product.
2. The method for preparing a bridged inclusion complex of β-cyclodextrin and resorcinol compounds according to claim 1, characterized in that, The bridged β-cyclodextrin is an epichlorohydrin cross-linked bridged β-cyclodextrin with a molecular weight of 5000-10000 Da and a purity of ≥98%.
3. The method for preparing a bridged inclusion complex of β-cyclodextrin and resorcinol compounds according to claim 1, characterized in that, The bridging β-cyclodextrin was dried under vacuum at 75–85°C for 1.5–2.5 h.
4. The method for preparing a bridged inclusion complex of β-cyclodextrin and resorcinol compounds according to claim 1, characterized in that, The molar ratio of bridged β-cyclodextrin to resorcinol compounds is 1:(0.7–1.1).
5. The method for preparing an inclusion complex of β-cyclodextrin and resorcinol compounds according to claim 1, characterized in that, In step S3, the power of the ultrasonic treatment is 140-190W and the frequency is 38-42kHz.
6. The method for preparing an inclusion complex of β-cyclodextrin and resorcinol compounds according to claim 1, characterized in that, In step S3, the amount of anhydrous ethanol used is 22-28 mL.
7. The method for preparing an inclusion complex of β-cyclodextrin and resorcinol compounds according to claim 1, characterized in that, In step S5, a Buchner funnel is used for filtration, and the washing volume of anhydrous ethanol and deionized water is 8-14 mL / time.
8. The method for preparing an inclusion complex of β-cyclodextrin and resorcinol compounds according to claim 1, characterized in that, In step S5, the sieve is 75-85 mesh.
9. The use of the inclusion complex of bridged β-cyclodextrin and resorcinol compounds as described in any one of claims 1-8 in the preparation of non-pharmaceutical antibacterial soothing skin care products.
10. The application according to claim 9, characterized in that, The antibacterial and soothing skin care product is a topical, non-medicinal product.